Nanoparticles are used to deliver anticancer drugs to solid tumors with leaky vasculature. However, clinical development of nanoparticles is challenging due in part to their limitations in physicochemical properties, such as low drug loading efficiency and poor circulation stability. Low drug loading not only causes technical difficulty in administration but also increases the amount of co-delivered carrier materials, imposing biological burdens to patients. Poor circulation stability causes loss of pharmacokinetics benefits of nanoparticles. To overcome these challenges, we developed albumin- coated nanocrystal (Abxtal) formulation of paclitaxel (PTX) with 90% drug loading and high serum stability. PTX-Abxtal was more stable in undiluted serum than Abraxane, a commercial albumin-based PTX nanoparticle formulation, maintained comparable cytotoxicity to those of Abraxane and solvent- dissolved PTX in vitro, and showed higher antitumor efficacy than Abraxane at the same dose in a mouse model of B16F10 melanoma. The investigators participated in the 2017-2018 Concept to Clinic: Commercializing Innovation (C3i) Program training with an ultimate goal to develop Abxtal formulation into drug products and identified that the most reasonable commercialization plan for the Abxtal technology is to license it out to innovator pharmaceutical companies with drug products near the end of their life cycle or competitor companies intending to develop new products with off-patent drug compounds. Toward this commercialization pathway, we propose to perform killer experiments identified during the C3i program training to accelerate translational development of the technology, using bortezomib and carfilzomib as alternative active ingredients. According to the preliminary results with PTX-Abxtal, it is expected that Abxtal formulations of bortezomib and carfilzomib will outperform the existing products substantially with respect to the drug distribution, efficacy, and toxicity profiles in preclinical models.
The proposed research is relevant to public health because a drug delivery strategy that increases deposition of nanomedicine in tumors to a greater extent than currently possible can enhance the efficacy of chemotherapy, minimize systemic side effects, prolong patient survival and improve their quality of life. Therefore, this research is consistent with the mission of the NIH, which pertains to developing resources that will assure the Nation?s capability to efficiently prevent and/or treat human diseases.
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